AFM13 is a first-in-class product for CD30-positive tumor types.
It will initially be developed in the high medical need salvage
setting of Hodgkin Lymphoma.

AFM13 – Hodgkin Lymphoma

Compound

Tumor Target

Effector Target

Indication

Discovery

Preclinical

Phase 1

Phase 2

Phase 3

AFM13

CD30

CD16A / NK-cell

Hodgkin Lymphoma

CD30+
Lymphoma

Hodgkin LymphomaCombination with CPIs*

Hodgkin LymphomaCombination with Lenalidomide

*CPI = Check Point Inhibitor

AFM13

AFM13 is a TandAb recognizing CD30 and utilizing its second functionality binds with high affinity to NK-cells and activates them. CD30 is overexpressed on Reed Sternberg cells that are the hallmark of Hodgkin Lymphoma (HL). In addition, CD30 is also expressed on a variety of T-cell lymphomas, including cutaneous T-cell lymphoma (CTCL) and anaplastic large cell lymphoma (ALCL). Furthermore, some 25% of Diffuse Large B-cell Lymphoma (DLBCL) patients carry the CD30 epitope. Overall, in North America, the EU and Japan, more than 50,000 patients are diagnosed annually with diseases in which malignant cells carry the CD30 epitope. Each year, between 6,000 t0 8,000 patients with these diseases relapse or become refractory to a series of standard treatments and require new therapeutic option.

Affimed has conducted a phase 1 dose escalation clinical trial in patients with relapsed / refractory HL. The clinical results have been presented to the medical community by Prof. Engert, the lead investigator for the study, at the Lugano International Meeting on Malignant Lymphoma in 2013. In sum, AFM13 has been found to be safe at the doses tested. Certain biomarkers indicated dose-dependent effects suggesting most active doses at or above 1.5 mg/kg. Anti-tumor activity was observed at all dose levels tested but was more pronounced at or above 1.5 mg/kg.

In this subgroup (N=13), 3 partial responses (≥50% tumor shrinkage) and 7 cases with stable disease were observed, resulting in an overall disease control rate of 77%. Of note, 6 of 7 patients that were refractory to brentuximab vedotin had a stabilization of their disease, an indication that this patient population may also benefit from AFM13 treatment. Based on these data a phase 2 study is being prepared with an optimized dosing regimen designed to demonstrate the full therapeutic potential of AFM13 in relapsed/refractory HL patients.

In August 2013, Affimed signed an agreement with the Leukemia and Lymphoma Society (LLS) under which LLS committed to co-fund up to $4.4 million over two years for the phase 2a development of AFM13. In doing so, the LLS recognized the critical need for safer and more durable therapies for HL. The LLS is committed to advancing breakthrough therapies, particularly for patients with unmet medical needs. The LLS is the world’s largest voluntary health agency dedicated to blood cancer; its mission is: cure leukemia, lymphoma, Hodgkin’s disease and myeloma, and improve the quality of life of patients and their families.

Medical Need in Hodgkin Lymphoma

Despite the advent of new therapies to treat HL patients that have relapsed, or not responded to earlier lines of therapy, the medical need remains high. Aside from some 34% of relapsed or refractory HL patients that appear to have a durable response with brentuximab vedotin, an antibody-drug conjugate recently introduced as HL salvage therapy to the market, the majority of patients – while initially responding to therapy - relapse within a few months and need to resort to experimental therapies.

This patient population comprises between 4,000 and 5,000 new cases every year in North America, the European Union and Japan. Affimed’s clinical data suggest that AFM13, due to its novel mode of action, may be active in these patients. This indication could provide a fast path to market.

We plan to explore whether AFM13 may not only be beneficial in the salvage setting, but also as part of a regimen that is applied earlier after diagnosis, where next to efficacy, safety is an important consideration for the choice of therapy. If clinical trials are successful AFM13 may ultimately achieve a place among earlier-line therapies, perhaps in combination with immunomodulators, tyrosine kinase inhibitors or with other biologics.

We plan to pursue AFM13 in other CD30-positive indications such as T-cell lymphoma, DLBCL and in other leukemias and lymphomas. CD30 expression has been shown to range between 100% and 25% in these diseases.